Studies were continued on the role of the liver as a source and modulator of circulating purines and pyrimidines. Compounds were studied in the isolated perfused rat liver in an attempt to dissociate the nucleoside export function of the liver from the uptake catabolic function. A potent inhibitor of pyrimidine nucleoside phosphorylase was found to substantially increase circulating concentrations of uridine. A GC/MS technique was developed to measure the flux through the de novo pyrimidine pathway in isolated hepatocytes and cultured cells in vitro and in normal and tumorous tissues in vivo by quantitating the incorporation of stable labelled precursors into the uracil nucleotide pool. The formation of di-labelled uracil molecules was exploited to quantitate the total flux through the de novo pathway which includes both labelled and non-labelled products. The inter-relationship of the urea cycle and the de novo pyrimidine pathway in isolated hepatocytes was investigated using isotopically labelled ammonia, glutamine, and bicarbonate. Circulating concentrations of uridine were found to inhibit de novo pyrimidine biosynthesis indicating that salvage of circulating pyrimidines is favored over de novo synthesis.